11-103283029-G-C

Position:

chr11-103283029-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001377.3(DYNC2H1):c.10834G>C(p.Asp3612His) variant causes a missense change. The variant allele was found at a frequency of 0.00671 in 1,602,214 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0063 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0068 ( 59 hom. )

Consequence

DYNC2H1
NM_001377.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 6.54

Variant links:

Genes affected

DYNC2H1 (HGNC:2962): (dynein cytoplasmic 2 heavy chain 1) This gene encodes a large cytoplasmic dynein protein that is involved in retrograde transport in the cilium and has a role in intraflagellar transport, a process required for ciliary/flagellar assembly. Mutations in this gene cause a heterogeneous spectrum of conditions related to altered primary cilium function and often involve polydactyly, abnormal skeletogenesis, and polycystic kidneys. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jan 2010]

DYNC2H1 links:

DYNC2H1 (HGNC:):

DYNC2H1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006396532).

BP6

Variant 11-103283029-G-C is Benign according to our data. Variant chr11-103283029-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 220403.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-103283029-G-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00628 (955/152112) while in subpopulation AMR AF= 0.0244 (373/15266). AF 95% confidence interval is 0.0224. There are 8 homozygotes in gnomad4. There are 482 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYNC2H1	NM_001080463.2 linkuse as main transcript	c.10855G>C	p.Asp3619His	missense_variant	74/90	ENST00000650373.2	NP_001073932.1	Q8NCM8-2
DYNC2H1	NM_001377.3 linkuse as main transcript	c.10834G>C	p.Asp3612His	missense_variant	73/89	ENST00000375735.7	NP_001368.2	Q8NCM8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYNC2H1	ENST00000650373.2 linkuse as main transcript	c.10855G>C	p.Asp3619His	missense_variant	74/90		NM_001080463.2	ENSP00000497174.1		Q8NCM8-2
DYNC2H1	ENST00000375735.7 linkuse as main transcript	c.10834G>C	p.Asp3612His	missense_variant	73/89	1	NM_001377.3	ENSP00000364887.2		Q8NCM8-1

Frequencies

GnomAD3 genomes

AF:

0.00629

AC:

956

AN:

151994

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00208

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0245

Gnomad ASJ

AF:

0.00577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.000755

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00650

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00789

AC:

1918

AN:

243014

Hom.:

AF XY:

0.00706

AC XY:

932

AN XY:

131968

show subpopulations

Gnomad AFR exome

AF:

0.00146

Gnomad AMR exome

AF:

0.0295

Gnomad ASJ exome

AF:

0.00533

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00251

Gnomad FIN exome

AF:

0.00159

Gnomad NFE exome

AF:

0.00654

Gnomad OTH exome

AF:

0.00716

GnomAD4 exome

AF:

0.00675

AC:

9791

AN:

1450102

Hom.:

Cov.:

AF XY:

0.00660

AC XY:

4753

AN XY:

720410

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.0275

Gnomad4 ASJ exome

AF:

0.00556

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00276

Gnomad4 FIN exome

AF:

0.00113

Gnomad4 NFE exome

AF:

0.00705

Gnomad4 OTH exome

AF:

0.00519

GnomAD4 genome

AF:

0.00628

AC:

955

AN:

152112

Hom.:

Cov.:

AF XY:

0.00648

AC XY:

482

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.00207

Gnomad4 AMR

AF:

0.0244

Gnomad4 ASJ

AF:

0.00577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.000755

Gnomad4 NFE

AF:

0.00650

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00612

Hom.:

Bravo

AF:

0.00744

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.00137

AC:

ESP6500EA

AF:

0.00738

AC:

ExAC

AF:

0.00688

AC:

831

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 14, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 27, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Asphyxiating thoracic dystrophy 3

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 02, 2023	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Jeune thoracic dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Short rib-polydactyly syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

T;T;.;.

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.89

.;D;.;D

MetaRNN

Benign

0.0064

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L;.;.

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-2.0

N;.;.;N

REVEL

Benign

0.26

Sift

Benign

0.041

D;.;.;D

Sift4G

Benign

0.11

T;.;.;T

Polyphen

0.066

B;B;P;P

Vest4

0.57

MVP

0.41

MPC

0.075

ClinPred

0.015

GERP RS

5.4

Varity_R

0.15

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over